{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:05:58Z","timestamp":1789477558079,"version":"build-2803163510"},"posted":{"date-parts":[[2026,5,4]]},"group-title":"HIV\/AIDS","reference-count":86,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["UM1 AI068614"],"award-info":[{"award-number":["UM1 AI068614"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["UM1 AI068635"],"award-info":[{"award-number":["UM1 AI068635"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["UM1 AI068618"],"award-info":[{"award-number":["UM1 AI068618"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["UM1 AI069412"],"award-info":[{"award-number":["UM1 AI069412"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["UL1 RR025758"],"award-info":[{"award-number":["UL1 RR025758"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["U54 AI170752"],"award-info":[{"award-number":["U54 AI170752"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01 AI145687"],"award-info":[{"award-number":["R01 AI145687"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["UM1 AI144371"],"award-info":[{"award-number":["UM1 AI144371"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["UM1 AI100645"],"award-info":[{"award-number":["UM1 AI100645"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Induction of broadly neutralizing antibodies (bnAbs) remains a major goal of HIV vaccine development. In a Phase I clinical trial, we evaluated the immunogenicity of CH505 transmitted\/founder (TF) envelope trimer designed to prime precursors of the heavy chain third complementarity determining region (CDRH3)-dominant class of CD4-binding site (CD4bs) HIV bnAbs. Neutralizing memory B-cell lineages were isolated from all vaccine recipients, including lineages targeting the CD4bs, V1\/V3, and gp120\/gp41 interface. Candidate CDRH3-dominant, CD4bs bnAb precursor lineages were identified in 73% of vaccinees, including one lineage that exhibited limited heterologous neutralization of global HIV-1 isolates. Structural analyses defined the modes of Env recognition by these three antibody classes. Together, these findings demonstrate that immunization with the CH505 TF trimer can prime a diverse, polyclonal repertoire of bnAb precursor lineages in humans, providing multiple starting points for sequential immunization strategies aimed at eliciting broadly neutralizing HIV-1 antibodies.<\/jats:p>\n                <jats:sec>\n                  <jats:title>HIGHLIGHTS<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>CH505 TF trimer immunogen induced autologous tier-2 neutralizing B cell lineages in all vaccine recipients.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>S365P-sensitive, CDRH3-dominant CD4-binding-site bnAb precursor candidates were detected in 73% of vaccinees.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>A single immunogen primed neutralizing antibody lineages targeting the CD4bs, V1\/V3, and gp120\/gp41 interface.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>High S365P-sensitive CD4bs responses were associated with distinct NK- and CD8\u207a T-cell states.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.02.26352058","type":"posted-content","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T22:20:15Z","timestamp":1777933215000},"source":"Crossref","is-referenced-by-count":1,"title":["Priming of Multiple HIV Neutralizing B Cell Precursors in Humans"],"prefix":"10.64898","author":[{"given":"Chen-Hao","family":"Yeh","sequence":"first","affiliation":[{"name":"Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 27710, USA"},{"name":"Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Boston, MA 02119, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth J.","family":"Parsons","sequence":"additional","affiliation":[{"name":"Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 27710, USA"},{"name":"Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyi E.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 27710, USA"},{"name":"Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, 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